To investigate the hypothesis that reflux of duodenal contents is a factor in pancreatic carcinogenesis, we developed a canine model to simultaneously quantify duodenal volume flow, pancreatic and duodenal pressures and reflux of duodenal contents into the pancreatic duct. We chose this model because our preliminary human studies suggested an association between separate openings of the pancreatic duct and common bile duct into the duodenum (as occurs in the dog) and abnormal ductal epithelium. Our objectives are to use this model to determine what physiologic events or pharmacologic manipulations might influence duodenal-pancreatic duct pressure relationships to cause reflux of duodenal contents into the pancreatic duct, to determine if flux occurs and, lastly, to determine if carcinogens reflux into the pancreatic duct and induce carcinogenesis. We have previously shown that pressure events occur postprandially which induce reflux of small amounts of duodenal contents into the pancreatic duct. Hormones may play a role in this phenomenon. Therefore, we plan to systematically examine the relationships between duodenal and pancreatic events and reflux under basal conditions and when intravenous secretin, CCK, glucagon, and gastrin are given separately or in combination. Secondly, to investigate the association between pancreatic carcinogenesis and cigarette smoking we will determine whether nicotine induces reflux of duodenal contents into the pancreatic duct, biliary and pancreatic clearances of an intravenously administered carcinogen, 14C-Benzanthracene, and whether the carcinogen will reflux into the pancreatic duct when perfused through the duodenum. Pending our ability to induce chronic reflux of duodenal contents into the pancreatic duct by either physiologic or pharmacologic means, we will attempt chronic studies utilizing perfusion of a carcinogen intraduodenally or by oral ingestion and maintenance of conditions which will promote chronic reflux of duodenal contents into the pancreatic duct. Our ultimate goal is to induce pancreatic carcinogenesis by the reflux mechanism.